Oxaliplatin, Capecitabine, and Cetuximab in Treating Patients With Advanced Liver Cancer (NRR)

Phase II Study of Oxaliplatin, Capecitabine, and Cetuximab in Advanced Hepatocellular Carcinoma

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving chemotherapy together with a monoclonal antibody may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving oxaliplatin and capecitabine together with cetuximab works in treating patients with advanced liver cancer.

Study Overview

• Status: Completed
• Conditions: Liver Cancer
• Intervention / Treatment: Biological: cetuximab; Drug: capecitabine; Drug: oxaliplatin

Detailed Description

OBJECTIVES:

Primary

• Determine the response rate in patients with advanced hepatocellular carcinoma and hepatic dysfunction treated with oxaliplatin, capecitabine, and cetuximab.

Secondary

• Determine the safety of this regimen in these patients.
• Determine the overall survival of patients treated with this regimen.
• Determine the time to tumor progression in patients treated with this regimen.

OUTLINE: This is an open label, nonrandomized study.

Patients receive oral capecitabine twice daily on days 1-14, cetuximab IV over 60-120 minutes on days 1, 8, and 15, and oxaliplatin IV over 120 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 3-4 weeks and then every 3 months thereafter.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7295
      • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Meets 1 of the following criteria:

  • Histologically confirmed hepatocellular carcinoma
  • Alpha-fetoprotein (AFP) > 400 ng/mL with compatible mass by CT scan or MRI
• Metastatic disease OR not a candidate for surgical resection or immediate liver transplantation
• At least 1 site of measurable disease OR evaluable disease (AFP 2 times upper limit of normal (ULN))
• No evidence of central nervous system (CNS) metastases (unless CNS metastases stable for > 3 months)

PATIENT CHARACTERISTICS:

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Absolute neutrophil count (ANC) ≥ 1,500/mm³
• Hemoglobin ≥ 9 g/dL
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ 3 times ULN
• International normalized ratio (INR) ≤ 1.5
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 times ULN
• Creatinine clearance > 50 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No known hypersensitivity to capecitabine, cetuximab, or oxaliplatin or to other murine products
• No comorbid condition which is deemed by the investigator to have a life expectancy of < 6 months
• No New York Heart Association class III-IV coronary artery disease and/or heart failure
• No variceal bleeding within the past 60 days
• No other cancer within the past 5 years except cervical intraepithelial neoplasia, nonmelanoma skin cancer, ductal carcinoma in situ, chronic lymphocytic leukemia, or treated localized prostate cancer with a normal prostate specific antigen level
• No active drug or alcohol abuse
• No prior allergic reaction to a therapeutic antibody
• No serious, uncontrolled infection
• No history of uncontrolled seizures, CNS disorders, or psychiatric disability that, in the opinion of the investigator, would preclude study participation or compliance
• No other serious uncontrolled medical condition that, in the opinion of the investigator, would preclude study participation
• No lack of physical integrity of the upper gastrointestinal tract
• No malabsorption syndrome
• No known existing uncontrolled coagulopathy

PRIOR CONCURRENT THERAPY:

• At least 4 weeks since prior participation in an investigational drug trial
• At least 4 weeks since prior major surgery and recovered
• At least 4 weeks since prior embolization, resection, or ablation
• No prior epidermal growth factor receptor (EGFR)-targeting therapy
• No prior systemic chemotherapy or hepatic artery infusion of chemotherapy
• No concurrent phenytoin

• No concurrent therapeutic warfarin

  • Low-dose non-therapeutic warfarin to maintain patency of venous access devices allowed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Single Arm Trial	Biological: cetuximab; 250 mg/m2, intravenously, once per week; Other Names: Erbitux; Drug: capecitabine; 850 mg/m2, orally, twice daily (dose rounded to accommodate 150 mg and 500 mg tablet sizes. Capecitabine given on days 1-14 of 21 day cycle.; Other Names: Xeloda; Drug: oxaliplatin; 130 mg/m2, intravenously on Day 1 of each 21 day cycle; Other Names: Eloxatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Response Rate	Radiographic response will be measured every six weeks while subject is on treatment. Response will be measured using RECIST criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions.	42 days (2 cycles)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects Experiencing Adverse Events	Adverse events will be assessed using CTCAE criteria.	every 3 weeks of treatment with an average of 15 weeks on treatment
Overall Survival	Overall survival will be calculated from time of enrollment to death or last contact date.	Median 23 month follow-up
Time to Progression	Time to progression will be calculated from the time of enrollment until confirmed disease progression. Defined by RECIST (Response Evaluation Criteria in Solid Tumors), Progressive Disease (PD) - at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.	Median 23 month follow-up

Collaborators and Investigators

• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Collaborators: Bristol-Myers Squibb; National Cancer Institute (NCI); Sanofi; Roche Pharma AG; National Center for Research Resources (NCRR)
• Investigators: Principal Investigator: Bert H. O'Neil, MD, UNC Lineberger Comprehensive Cancer Center; Principal Investigator: Michael A. Morse, MD, Duke University

Publications and helpful links

General Publications

• Sanoff HK, Bernard S, Goldberg RM, Morse MA, Garcia R, Woods L, Moore DT, O'Neil BH. Phase II Study of Capecitabine, Oxaliplatin, and Cetuximab for Advanced Hepatocellular Carcinoma. Gastrointest Cancer Res. 2011 May;4(3):78-83.

Helpful Links

• University of North Carolina Lineberger Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: October 1, 2006
• Primary Completion (Actual): February 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: June 6, 2007
• First Submitted That Met QC Criteria: June 6, 2007
• First Posted (Estimate): June 7, 2007

Study Record Updates

• Last Update Posted (Actual): July 12, 2017
• Last Update Submitted That Met QC Criteria: June 13, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: advanced adult primary liver cancer; recurrent adult primary liver cancer; localized unresectable adult primary liver cancer; adult primary hepatocellular carcinoma
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Capecitabine; Oxaliplatin; Cetuximab
• Other Study ID Numbers: LCCC 0421; KL2RR025746 (U.S. NIH Grant/Contract); 5K23CA118431-02 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No